Vidal Essebag

Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation

BACKGROUND Many patients requiring pacemaker or implantable cardioverter-defibrillator (ICD) surgery are taking warfarin. For patients at high risk for thromboembolic events, guidelines recommend bridging therapy with heparin; however, case series suggest that it may be safe to perform surgery without interrupting warfarin treatment. There have been few results from clinical trials to support the safety and efficacy of this approach. METHODS We randomly assigned patients with an annual risk of thromboembolic events of 5% or more to continued warfarin treatment or to bridging therapy with heparin. The primary outcome was clinically significant device-pocket hematoma, which was defined as device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery (e.g., hematoma evacuation). RESULTS The data and safety monitoring board recommended termination of the trial after the second prespecified interim analysis. Clinically significant device-pocket hematoma occurred in 12 of 343 patients (3.5%) in the continued-warfarin group, as compared with 54 of 338 (16.0%) in the heparin-bridging group (relative risk, 0.19; 95% confidence interval, 0.10 to 0.36; P<0.001). Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade and one myocardial infarction in the heparin-bridging group and one stroke and one transient ischemic attack in the continued-warfarin group. CONCLUSIONS As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma. (Funded by the Canadian Institutes of Health Research and the Ministry of Health and Long-Term Care of Ontario; BRUISE CONTROL ClinicalTrials.gov number, NCT00800137.).

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis

Background— Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. Methods and Results— We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78–1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13–1.85) after adjusting for potential confounders. Propensity score–adjusted analyses yielded similar results. Conclusions— Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

Discerning the incidence of symptomatic and asymptomatic episodes of atrial fibrillation before and after catheter ablation (DISCERN AF): a prospective, multicenter study.

BACKGROUND The DISCERN AF study (Discerning Symptomatic and Asymptomatic Episodes Pre and Post Radiofrequency Ablation of Atrial Fibrillation) monitored atrial fibrillation (AF) using an implantable cardiac monitor (ICM) to assess the incidence and predictors of asymptomatic AF before and after catheter ablation. METHODS Patients with symptomatic AF underwent implantation of an ICM with an automated AF detection algorithm 3 months before and 18 months after ablation. Patients kept a standardized diary to record symptoms of arrhythmia, and ICM data were downloaded every 3 months. All episodes were blindly adjudicated and correlated with the diary. Asymptomatic recurrences were ICM episodes of 2 minutes or longer with no associated diary symptoms. RESULTS Fifty patients had 2355 ICM episodes. Of these, 69.0% were true AF/atrial flutter (AFL)/atrial tachycardia (AT); 16.0%, sinus with extrasystoles; 11.0%, artifact; and 4.0%, sinus arrhythmia. Total AF/AFL/AT burden was reduced by 86% from a mean (SD) of 2.0 (0.5) h/d per patient before to 0.3 (0.2) h/d per patient after ablation (P < .001), and 56.0% of all episodes were asymptomatic. The ratio of asymptomatic to symptomatic AF episodes increased after ablation from 1.1 to 3.7 (P = .002). By symptoms alone, 29 of 50 patients (58%) were free of AF/AFL/AT after ablation compared with 23 of 50 (46%) using ICM-detected AF/AFL/AT recurrence. Asymptomatic episodes were more likely AFL/AT and were significantly shorter and slower, with lower heart rate variability. However, the postablation state was the strongest independent predictor of asymptomatic AF. CONCLUSIONS The ratio of asymptomatic to symptomatic AF episodes increased from 1.1 before to 3.7 after ablation. Postablation state is the strongest predictor of asymptomatic AF. Symptoms alone underestimate postablation AF burden, with 12% of patients having asymptomatic recurrences only. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00745706.

Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs

BACKGROUND Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. METHODS We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. RESULTS Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. CONCLUSIONS In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).

The nested case-control study in cardiology.

BACKGROUND The nested case-control study is an efficient epidemiological design whereby a case-control approach is employed within an established cohort. The large number of recent prospective studies and randomized trials conducted in cardiology provide cohorts within which the nested case-control approach is increasingly used. METHODS This paper describes the design of the nested case-control study, and evaluates its role in cardiology by reviewing all such studies indexed in Medline from 1966 to 2000. The example of homocysteine is used to illustrate how discrepancies between results of nested case-control and case-control studies played an important role in the decisions and recommendations of national and international organizations. RESULTS Seventy-seven nested case-control studies in cardiology were reviewed. The number of studies per year has been increasing since the first publication in 1987. The majority (96%) of studies evaluated potential risk factors for cardiovascular disease while the remainder evaluated drugs with cardiac adverse effects. In studies of homocysteine and coronary artery disease, nested case-control studies did not confirm the strong association suggested by early case-control studies that may have been influenced by bias (eg, selection, publication, or reverse causality). This led national and international organizations to advise against routine screening. CONCLUSIONS The nested case-control study is increasingly used to study causal relationships in cardiology. The large cohorts of cardiac patients created by prospective studies, clinical trials, and administrative databases should be exploited using this methodology to assess potential cardiac risk factors and other causal relationships that cannot be studied in randomized trials.

Healthcare Resource Utilization and Costs Associated with Recurrent Episodes of Atrial Fibrillation: The FRACTAL Registry

Introduction: Drivers of cost in the atrial fibrillation (AF) population are not fully understood. We sought to characterize the resource utilization and costs of treating new‐onset AF, with emphasis on the incremental costs associated with recurrent episodes of AF over time.

Left atrial function and scar after catheter ablation of atrial fibrillation

BACKGROUND Catheter ablation of atrial fibrillation (AF) involves extensive radiofrequency ablation (RFA) of the left atrium (LA) around the pulmonary veins. The effect of this therapy on LA function is not fully characterized. OBJECTIVE The purpose of this study was to determine whether catheter ablation of AF is associated with a change in LA function. METHODS LA and right atrial (RA) systolic function was assessed in 33 consecutive patients with paroxysmal or persistent AF referred for ablation using cardiovascular magnetic resonance (CMR) imaging. Steady-state free precession ECG cine CMR imaging was performed before and after (mean 48 days) AF ablation. All patients underwent circumferential pulmonary vein isolation using an 8-mm tip RFA catheter. High spatial resolution late gadolinium enhancement CMR images of LA scar were obtained in 16 patients. RESULTS Maximum LA volume decreased by 15% (P <.001), and LA ejection fraction decreased by 14% (P <.001) after AF ablation. Maximum RA volume decreased by 13% (P = .018), but RA ejection fraction increased by 5% (P = .008). Mean LA scar volume was 8.1 +/- 3.7 mL. A linear correlation was observed between change in LA ejection fraction and scar volume (r = -0.75, P <.001). CONCLUSION Catheter ablation of AF is associated with decreased LA size and reduced atrial systolic function. This change strongly correlates with the volume of LA scar. This finding may have implications for postprocedural thromboembolic risk and for procedures involving more extensive RFA.

Comparative Effectiveness of Rhythm Control vs Rate Control Drug Treatment Effect on Mortality in Patients With Atrial Fibrillation

BACKGROUND Controversy continues concerning the choice of rhythm control vs rate control treatment strategies for atrial fibrillation (AF). A recent clinical trial showed no difference in 5-year mortality between the 2 treatments. We aimed to determine whether the 2 strategies have similar effectiveness when applied to a general population of patients with AF with longer follow-up. METHODS We used population-based administrative databases from Quebec, Canada, from 1999 to 2007 to select patients 66 years or older hospitalized with an AF diagnosis who did not have AF-related drug prescriptions in the year before the admission but received a prescription within 7 days of discharge. Patients were followed until death or administrative censoring. Mortality was analyzed by multivariable Cox regression. RESULTS Among 26,130 patients followed for a mean (SD) period of 3.1 years (2.3 years), there were 13,237 deaths (49.5%). After adjusting for covariates, we found that the effect of rhythm vs rate control drugs changed over time: after a small increase in mortality for patients treated with rhythm control in the 6 months following treatment initiation (hazard ratio [HR], 1.07; 95% CI, 1.01-1.14), the mortality was similar between the 2 groups until year 4 but decreased steadily in the rhythm control group after year 5 (HR, 0.89; 95% CI, 0.81-0.96; and HR, 0.77; 95% CI, 0.62-0.95, after 5 and 8 years, respectively). CONCLUSIONS In this population-based sample of patients with AF, we found little difference in mortality within 4 years of treatment initiation between patients with AF initiating rhythm control therapy vs those initiating rate control therapy. However, rhythm control therapy seems to be superior in the long-term.

Clinical Predictors of Fidelis Lead Failure Report From the Canadian Heart Rhythm Society Device Committee

Background— Approximately 268 000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study. Methods and Results— A total of 3169 Sprint Fidelis leads were implanted in 11 centers with a total of 251 failures. Lead failure rates at 3, 4, and 5 years were 5.3%, 10.6%, and 16.8%, respectively. The rate of lead failure continues to accelerate (P<0.001). There were 4 independent predictors of failure: center, sex, access vein, and previous lead failure. Women had a higher hazard of failure (hazard ratio 1.51; 95% confidence interval, 1.14–2.04; P=0.005). Both axillary and subclavian access increased the hazard of failure (P=0.007); hazard ratio for axillary was 1.94, (95% confidence interval, 1.23–3.04) and for subclavian 1.63 (95% confidence interval, 1.08–2.46). Previous lead failure increased the hazard of a subsequent Fidelis failure with a hazard ratio of 3.12 (95% confidence interval, 1.80–5.41; P<0.001). Conclusions— The rate of Fidelis failure continues to increase over time, with failures approaching 17% at 5 years. Women, patients with leads inserted via the subclavian or axillary vein, and those with a previous lead fracture were at greatest risk of Fidelis failure. Our data suggest that Fidelis replacement should be strongly considered at the time of generator replacement.Background— Approximately 268 000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study. Methods and Results— A total of 3169 Sprint Fidelis leads were implanted in 11 centers with a total of 251 failures. Lead failure rates at 3, 4, and 5 years were 5.3%, 10.6%, and 16.8%, respectively. The rate of lead failure continues to accelerate ( P <0.001). There were 4 independent predictors of failure: center, sex, access vein, and previous lead failure. Women had a higher hazard of failure (hazard ratio 1.51; 95% confidence interval, 1.14–2.04; P =0.005). Both axillary and subclavian access increased the hazard of failure ( P =0.007); hazard ratio for axillary was 1.94, (95% confidence interval, 1.23–3.04) and for subclavian 1.63 (95% confidence interval, 1.08–2.46). Previous lead failure increased the hazard of a subsequent Fidelis failure with a hazard ratio of 3.12 (95% confidence interval, 1.80–5.41; P <0.001). Conclusions— The rate of Fidelis failure continues to increase over time, with failures approaching 17% at 5 years. Women, patients with leads inserted via the subclavian or axillary vein, and those with a previous lead fracture were at greatest risk of Fidelis failure. Our data suggest that Fidelis replacement should be strongly considered at the time of generator replacement. # Clinical Perspective {#article-title-32}

Complications Associated With Revision of Sprint Fidelis Leads Report From the Canadian Heart Rhythm Society Device Advisory Committee

Background— It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously. Methods and Results— Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P=0.0008). Conclusions— The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.